EFFECTS OF TREADMILL EXERCISE ON THE EXPRESSION OF NETRIN-1 AND ITS RECEPTORS IN RAT BRAIN AFTER CEREBRAL ISCHEMIA
EFFECTS OF TREADMILL EXERCISE ON THE EXPRESSION OF NETRIN-1 AND ITS RECEPTORS IN RAT BRAIN AFTER CEREBRAL ISCHEMIA
复制标题
DOI：
10.1016/j.neuroscience.2011.07.037
复制
发表时间：
2011-10-27
期刊：
影响因子：
3.3
通讯作者：
Du, H.
中科院分区：
文献类型：
--
作者：
Liu, N.;Huang, H.;Du, H.
最近的证据表明，运动改善脑缺血动物模型的功能结果。由于netrin-1及其受体，在结肠直肠癌（DCC）和不协调基因58（Unc 5 B）中缺失，作为神经和血管活动的重要调节因子，我们试图确定netrin-1和DCC和Unc 5 B是否参与运动对诱导脑缺血大鼠的神经保护作用。将108只大鼠随机分为3组：假手术组（n=12）、大脑中动脉闭塞（MCAO）组（n=48）、MCAO+跑台运动组（n=48）。行为学测试结果显示，跑台运动可显著改善脑缺血大鼠在缺血后14、28 d的神经功能缺损（n=12，P < 0.05和P < 0.01），但在4、7 d时无显著性差异。定量逆转录聚合酶链反应（qPCR）和Western blot分析显示，运动可增加大鼠缺血周围脑区netrin-1和DCC的表达，而抑制Unc 5 B的表达，尤其是在MCAO后14和28天（n=4，P < 0.05或P < 0.01）。免疫荧光分析显示，在缺血周围区，netrin-1主要表达于神经元胞体，DCC主要表达于神经突起和血管周围星形胶质细胞，Unc 5 B主要表达于神经元胞体和部分突起。这些结果表明，netrin-1及其受体DCC和Unc 5 B可能参与运动诱导的缺血周围区神经回路重塑，运动可能通过调节netrin-1 Unc 5 B信号通路促进该区域神经元的存活。此外，netrin-1也可能通过DCC免疫反应性笔血管星形胶质细胞在脑血屏障中发挥作用。总之，我们表明，跑步机运动具有有益的影响，这可能是由于，至少部分地，netrin-1及其受体DCC和Unc 5 B在脑缺血大鼠的神经元和血管活动的参与。(C)2011年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Recent evidence suggests that exercise improves functional outcome in animal models of cerebral ischemia. Since netrin-1 and its receptors, deleted in colorectal cancer (DCC) and uncoordinated gene 58 (Unc5B), act as important regulators in neural and vascular activities, we sought to determine whether netrin-1 and DCC and Unc5B are involved in the neuroprotective effects of exercise on rats with induced cerebral ischemia. A total of 108 rats were randomly distributed into three groups: sham-operated group (n=12), middle cerebral artery occlusion (MCAO) group (n=48), MCAO+treadmill exercise group (n=48). Behavioral testing indicated that treadmill exercise could significantly improve neurologic deficits of rats with cerebral ischemia at day 14 and 28 after MCAO (n=12, P < 0.05 and P < 0.01), but there was no significant difference at day 4 and 7. Quantitative reverse transcription polymerase chain reaction (qPCR) and Western blot analysis revealed that treadmill exercise enhanced netrin-1 and DCC expression, while it suppressed Unc5B expression in rat peri-ischemic brain area, especially at day 14 and 28 after MCAO (n=4, P < 0.05 or P < 0.01). Immunofluorescence analysis showed that in the peri-ischemic area, netrin-1 was expressed in neuronal perikarya, DCC, however, was expressed in neural processes and pen-vascular astrocytes, while Unc5B was expressed mostly in neuronal perikarya and some processes. These results suggest that netrin-1 and its receptors DCC and Unc5B may engage in exercise-induced neural circuit remodeling in the peri-ischemic area, and exercise may promote survival of neurons in this area by regulating netrin-1 Unc5B signaling. Additionally, netrin-1 may also play a role in brain blood barrier via DCC-immunoreactive pen-vascular astrocytes. In conclusion, we demonstrate that treadmill exercise has beneficial effects that may be attributed, at least in part, to the involvement of netrin-1 and its receptors DCC and Unc5B in the neuronal and vascular activities in brain-ischemic rats. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.